FDA Releases Work Plan Implementing the 21st Century Cures Act
As the focus on passing user fee legislation continues, the US Food and Drug Administration (FDA) has been moving ahead with implementation of the 21st Century Cures Act (Cures Act), which was enacted in December 2016 following a multi-year, bipartisan effort to accelerate the pace of the discovery, development, and delivery of new treatments and cures.1 Title III of the Cures Act provides the FDA with new authorities aimed at enhancing and accelerating FDA's processes for reviewing and approving new drugs, biologics, and medical devices. The law also authorizes an additional $500 million over 10 years to an FDA Innovation Account to help the Agency carry out these new authorities.2
On July 7, 2017, FDA made public its Work Plan3 and list of deliverables,4 which provide more detail on how the Agency will allocate the new Innovation Account funds to implement Title III of the Cures Act. Although 37 provisions of the Cures Act are eligible for FDA Innovation Account funds,5 the Agency has initially proposed to limit additional funding to 22 Cures Act provisions, giving priority to provisions that:
- present the greatest opportunity for the FDA to foster innovation and integrate advances in biological sciences, engineering, information technology, and data science, to most directly improve the Agency's product review tools and processes;
- address the greatest need for scientific modernization;
- have the most immediate impact on delivery of services; and
- have no other source of funding.
As such, certain Cures Act provisions for which FDA has determined that additional funding is not required—such as Secs. 3034 and 3035, which require the FDA to issue guidance and a Congressional report on regenerative therapies—would not receive Innovation Account funds. The FDA, however, plans to take a "flexible approach" to implementing the Cures Act, and will reassess the allocation of Innovation Account funds each appropriations cycle.
This Advisory provides an overview of FDA's proposed allocation of Innovation Account funds from FY 2017 to 2025.
Subtitle A—Patient-Focused Drug Development
The Work Plan proposes allocating a total of $25.8 million from the FDA Innovation Account, over fiscal year (FY) 2018 to FY 2025, to implement the following sections of Subtitle A:
- Sec. 3001. Patient Experience Data
- Sec. 3002. Patient-Focused Drug Development Guidance
- Sec. 3004. Report on Patient Experience Drug Development
These sections require the FDA to issue a statement on patient experience data submitted and reviewed as part of an application, to issue guidance on the collection and use of patient experience data, and to issue a report on the use of patient experience data in regulatory decisionmaking. The Work Plan states that Innovation Account funds would help facilitate a more "systematic gathering" and use of patients' perspectives. FDA proposes strengthening its staff with clinical, statistical, psychometric, and health outcomes research expertise, and incorporating such staff into review teams where sponsors intend to use patient experience data. The Work Plan also describes the development of guidance on patient experience data as a "top priority" for the Agency, though it notes that the FDA intends to primarily rely on Prescription Drug User Fee Act (PDUFA) VI fee funding to support its guidance development work.
Subtitle B—Advancing New Drug Therapies
FDA proposes allocating a total of $95.3 million of the FDA Innovation Account funds, over FY 2017 through 2025, to implement Subtitle B. The Agency would use the funds to implement the following provisions:
- Sec. 3001. Qualification of Drug Development Tools. This section requires the Secretary to establish a process for qualification of drug development tools (e.g., biomarkers, clinical outcomes assessments) for use in supporting or obtaining FDA approval for, or investigational use of, a drug or biologic. The Work Plan states that Innovation Account funds would support expert FDA staff and contractors who are needed to help develop the evidentiary criteria to support qualification, development of regulatory informatics platforms, and to integrate new review processes.
- Sec. 3012. Targeted Drugs for Rare Diseases. This section intends to facilitate the development, review, and approval of "genetically targeted drugs" and "variant protein targeted drugs" that would address an unmet need in one or more patient subgroups with respect to rare diseases or conditions that are serious or life-threatening. This section permits the Secretary to allow the sponsor of a drug or biologic application for a genetically targeted drug or variant protein targeted drug to rely on information previously submitted by the same sponsor, or in limited circumstances another sponsor (i.e., where there is a right of reference), in another application. The Work Plan states that expert FDA staff will be needed to support the review activities.
- Sec. 3013. Reauthorization of Program to Encourage Treatments for Rare Pediatric Diseases. This section reauthorizes the pediatric rare disease priority review program until 2020. Under the Work Plan, from FY 2018 to 2020, expert FDA staff are needed to develop guidance, review rare pediatric disease designation requests, improve IT and other systems, and to manage the administration of the program.
- Sec. 3016. Grants for Studying Continuous Manufacturing. This section permits the Secretary to issue grants for the purpose of studying and recommending improvements to the processes of continuous manufacturing for drugs and biological products. Under the Work Plan, expert FDA staff would issue grants and develop well-defined scientific standards and policies for articulating how the Agency would evaluate these technologies as part of submissions for new drugs, generic drugs, biotechnology products, and biosimilars.
Subtitle C—Modern Trial Design and Evidence Development
The Work Plan proposes allocating $57.8 million of the FDA Innovation Account funds, over FY 2017 to 2025, to implement Subtitle C. The Agency would use the funds to implement the following provisions:
- Sec. 3021. Novel Clinical Trial Designs. This section requires the Secretary to convene a public meeting and to issue guidance for the purpose of assisting sponsors in incorporating complex adaptive and other novel trial designs into proposed clinical protocols and applications for new drugs and biologics. The Work Plan states that FDA expert staff are needed to plan and conduct the public meeting, to further develop novel clinical trial designs and approaches, and to draft the guidance.
- Sec. 3022. Real World Evidence. This section requires the Secretary to establish a program to evaluate the potential use of "real world evidence" to support approval of a new indication for an already approved drug or to help support or satisfy post-approval study requirements. The Cures Act defines "real world evidence" as "data regarding the usage, or the potential benefits or risks, of a drug derived from sources other than randomized clinical trials." The Work Plan states that FDA staff with expertise in statistics, data science, meta-analysis, clinical outcomes research, and other areas are needed to develop the framework and methodologies for evaluating the use of real world evidence. Such staff would also draft guidance and hold a workshop on using real world evidence in regulatory decisionmaking.
- Sec. 3023. Protection of Human Research Subjects. This section requires the Secretary to "harmonize" the differences between the HHS Human Subject regulations (Common Rule) and the FDA Human Subject regulations. The Work Plan proposes using staff experienced with the rulemaking and harmonization process to help implement this section.
- Sec. 3024. Informed Consent Waiver or Alteration for Clinical Investigations. This section gives FDA the authority to waive or alter informed consent requirements for certain clinical trials with "minimal risk." The Work Plan states that the FDA will need highly experienced staff to help revise FDA regulations and to issue guidance.
Subtitle D—Patient Access to Therapies and Information
The Work Plan proposes $185.2 million from the FDA Innovation Account, over FY 2017 to 2025, to implement Subtitle D. Such funds would be used to implement the following sections:
- Sec. 3031. Summary Level Review. This section permits the Secretary to rely upon "qualified data summaries" to support approval of a supplemental application for a qualified use of a drug or biologic. As the FDA's initial focus in implementing this provision will be on supplemental applications for cancer drugs, the Work Plan proposes that staff in the Oncology Center of Excellence would develop policies and procedures for implementing summary level review for appropriate oncology applications for drugs and biologics.
- Sec. 3033. Accelerated Approval of Regenerative Advanced Therapies. This section establishes a program under which sponsors could seek Regenerative Medicine Advanced Therapy (RMAT) designation for their products. Upon designation, the sponsor is eligible for earlier interactions with the FDA, and would be eligible for priority review or accelerated approval. The FDA Work Plan states that the Center for Biologics Evaluation and Research (CBER) would need to provide continual RMAT training for all Center staff who work on these products.
- Sec. 3036. Standards for Regenerative Medicine and Regenerative Advanced Therapies. This section requires the Secretary, in consultation with the National Institute of Standards and Technology and other stakeholders, to develop standards and consensus definition of terms to support the development and review of regenerative medicine therapies and regenerative advanced therapies. The Work Plan proposes using Innovation Account funds to support FDA staff and to facilitate the public collaboration with NIST and other stakeholders. The FDA intends to foster public-private partnerships that would facilitate long-term engagement with stakeholders.
- Sec. 3038. Combination Product Innovation. This section reforms FDA's approval processes for combination products, including establishing standards for interagency coordination. It also requires FDA to issue guidance on pre-submission interactions between the Agency and sponsors of combination products. To implement this section, the Work Plan states that FDA staff would need to: conduct assessments of existing policies, procedures, and IT systems and make necessary modifications; establish new tracking systems; and support program implementations. Staff would also need to develop and revise guidance documents, regulations, notices, standard operating procedures, trainings, and other tools.
Subtitle F—Medical Device Innovation
The Work Plan proposes allocating $109 million from the FDA Innovation Account, over FY 2017 to 2025, to implement Subtitle F. The funds would be used to implement the following sections of the Cures Act:
- Sec. 3051. Breakthrough Devices. This section requires the Secretary to establish a pathway for the "efficient and flexible" review of "devices that represent breakthrough technologies." FDA estimates that this program will grow at a rate that could approach 20 percent per year over the next 10 years. As the program requires frequent and extensive interaction between developers and FDA staff during the device development phase, the Work Plan states that the FDA will need to accommodate the increased workload and will need to acquire certain IT systems.
- Sec. 3052. Humanitarian Device Exemption. This section gives the Secretary the authority to apply the humanitarian device exemption to devices that treat diseases and conditions that affect up to 8,000 individuals in the United States (prior cap was 4,000 individuals). The Work Plan states that FDA staff would be needed to accommodate the increased workload. Additionally, the Agency would need to acquire IT systems and track the impact of this section on the development of devices for rare diseases and conditions.
- Sec. 3053. Recognition of Standards. This section establishes a process at the FDA for the submission, review, and recognition of standards established by nationally or internationally recognized standards organizations for purposes of medical device review. The Work Plan states that FDA expert staff would be needed to coordinate review of submitted standards and to respond to external information requests. The Agency would also need operating funds to support travel for FDA to participate in a greater number of national and international standard-setting organization meetings.
- Sec. 3056. Institutional Review Board Flexibility. This section eliminates the requirement that a sponsor of a medical device trial must always use a local institutional review board (IRB). FDA Innovation Account funds would support the development of key guidance documents on the use of centralized IRBs.
- Sec. 3058. Least Burdensome Device Review. This section requires the FDA to train employees on the meaning and implementation of the least burdensome requirements, and for the Agency to audit the implementation. Funds would be used to support FDA expert staff and contractors to conduct these audits.
- Sec. 3060. Clarifying Medical Device Software. This section exempts from FDA regulation-specific categories of software based on their low levels of risk to patients. Innovation Account funds would be used to support FDA expert staff in implementing a system for surveillance of exempted products or functions.
Subtitle G—Improving Scientific Experience and Outreach at FDA
The Work Plan proposes allocating $27 million of the FDA Innovation Accounts, from FY 2018 to 2025, to implement Sec. 3073, which requires the FDA to establish one or more Intercenter Institutes for a major disease area or areas. The FDA has already established the first Intercenter Institute—the Oncology Center of Excellence (OCE), which enables a unified policy approach and clinical review of all drugs, biologics, and devices used in medical oncology. The Innovation Funds would support FDA medical and professional staff's coordinated review of oncology product applications across the medical product centers, policy development, and collaboration with external stakeholders.
If you have any questions regarding the implementation of the Cures Act, please do not hesitate to contact us.
© 2017 Arnold & Porter Kaye Scholer LLP. This Advisory is intended to be a general summary of the law and does not constitute legal advice. You should consult with counsel to determine applicable legal requirements in a specific fact situation.